神经保护剂在脑缺血再灌注的治疗中具有重要作用。Hsp20在脑组织中表达水平较高，丝氨酸残基的磷酸化是Hsp20转录后修饰的主要方式。我们前期研究发现，Hsp20在脑缺血再灌注中对神经细胞具有保护作用，其神经保护作用与Ser16磷酸化密切相关。我们同时发现，脑缺血再灌注后，线粒体出现碎裂，细胞色素C释放增加；高尔基体同样也发生了碎裂。线粒体与高尔基体在脑缺血再灌注损伤中具有至关重要的作用，它们是神经保护的良好靶点。而Hsp20则能减轻缺血再灌注后线粒体的碎裂，抑制细胞色素C的释放，保护线粒体是其神经保护作用的重要机制。因此，在本研究中，我们将在前期研究基础上，通过体内外实验，系统研究Hsp20表达及磷酸化水平与脑缺血再灌注损失的相关性，Hsp20在脑缺血再灌注损伤中的神经保护作用及与Ser16磷酸化的关系，Hsp20及其磷酸化突变体对线粒体高尔基体的保护作用，为其早日应用于临床治疗奠定基础。

Neuroprotective agents play an important role in the treatment of cerebral ischemia-reperfusion injury. Hsp20 is highly and constitutively expressed in the brain. Phosphorylation at serine residues is a major post-translational modification that occurs to Hsp20. In previous studies, our data demonstrated that increased Hsp20 expression in neuronal cells protected against ischemia-reperfusion injury. Phosphorylation of Ser16 played an important role in the neuroprotective effect of Hsp20. We also demonstrated that cerebral ischemia-reperfusion injury induced mitochondria fragmentation and the release of cytochrome c from mitochondria to cytosol. Meanwhile, the Golgi apparatus also showed fragmentation. Mitochondria and the Golgi apparatus are crucial in cerebral ischemia-reperfusion injury and they are potential targets for neuroprotective interventions. Our results suggested that Hsp20 alleviated ischemia-reperfusion-induced mitochondria fragmentation and decreased the release of cytochrome c from mitochondria to cytosol. The protective action on mitochondria may account for its neuroprotective actions. Therefore, on the basis of our previous findings, we will investigate the expression pattern of Hsp20 and its phosphorylation upon cerebral ischemia-reperfusion injury both in vitro and in vivo. We will also define the functional significance of the nonphosphorylated and phosphorylated Hsp20 forms in neuroprotection on cerebral ischemia-reperfusion injury. Finally, we will study the potential benefits of Hsp20 and its phosphorylation form action on mitochondria and the Golgi apparatus and the underlying mechanism(s). Thus, these findings will provide experimental and therapeutic options for the treatment of a broad range of pathologic disorders associated with cerebral ischemia-reperfusion injury.